We perform in depth analyses of the immune response to multiple different vaccines and to multiple different natural viral infections in order to dissect those immune responses that mediate protection from viral infection or dissemination. Antigen presenting cells are tracked from the time of vaccination to determine where and how they present antigen, and in what context, to B and T cells in the lymph nodes. The effects of chronic immune activation and antigen stimulation on the immune response to different pathogens are studied. In addition, the effects of HIV infection on different pathogen-specific T cell responses are evaluated.